crossing96/oncoscreening huggingface dataset:
Circular RNA FAM114A2 suppresses progression of bladder cancer via regulating ∆NP63 by sponging miR-762.	Numerous evidences have shown that circular RNAs (circRNAs) play a key role in regulating the pathogenesis of cancer. However, the mechanism of circRNAs in urothelial carcinoma of bladder (UCB) remains largely unclear. In this study, we found circFAM114A2 was significantly downregulated both in UCB tissue specimens and cell lines, and the expression level was highly correlated with pathological TNM stage and grade. Functionally, overexpression of circFAM114A2 dramatically inhibited the migration, invasion and proliferation of UCB cells in vitro, and suppressed tumor growth in vivo. Mechanistically, we confirmed miR-762 was copiously pulled down by circFAM114A2 in 5637 and T24 cells. Fluorescence in situ hybridization (FISH) further indicated the cytoplasmic interactions between circFAM114A2 and miR-762. By using luciferase reporter assay, we found that miR-762 could directly target TP63. Subsequently, we found that circFAM114A2 might increase the expression of ∆NP63 (main isoform of TP63 in UCB) by sponging miR-762. Taken together, our results demonstrated that circFAM114A2 might serve as a competing endogenous RNA (ceRNA) of miR-762 in regulating the expression of ∆NP63, thus suppressed UCB progression through circFAM114A2/miR-762/∆NP63 axis.	bladder
p62 promotes bladder cancer cell growth by activating KEAP1/NRF2-dependent antioxidative response.	p62 is associated with 2 major cellular defense mechanisms against metabolic and oxidative stress, autophagy and the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor-E2-related factor 2 (NRF2) system. Recent studies indicate that the p62-KEAP1-NRF2 pathway promotes tumorigenesis and tumor growth mediated by NRF2-dependent antioxidative response. However, whether p62 is involved in bladder cancer (BCa) development remains unknown. Here, we found that p62 is overexpressed in BCa tissue and several BCa cell lines. The knockdown of p62 inhibits BCa cell growth both in vitro and in vivo, with increased intracellular reactive oxygen species level. Mechanically, p62 activates NRF2 signaling by sequestrating KEAP1, which leads to the upregulation of antioxidant genes (Gclc, Gstm5, and Gpx2), thus protecting BCa cells from oxidative stress. Our findings indicate that p62 might be involved in the development of BCa and serve as a potential therapeutic target.	bladder
Blood transfusions during neoadjuvant chemotherapy for muscle-invasive urinary bladder cancer may have a negative impact on overall survival.	Objective: To evaluate the extent and plausible effects of blood transfusions given during cisplatin-based neoadjuvant chemotherapy (NAC) on overall survival in patients with muscle-invasive urothelial bladder cancer (MIBC) undergoing NAC and radical cystectomy (RC).Background: Several studies have demonstrated a decreased survival for MIBC patients receiving allogenic peri- and postoperative blood transfusions in conjunction with RC. No studies have previously investigated the effects of blood transfusions during NAC.Materials and methods: 120 patients with MIBC (cT2-T4aN0M0) undergoing NAC and RC between 2008 and 2014 at four Swedish cystectomy centers were retrospectively evaluated. Clinicopathological data were obtained, including data of allogenic blood administration. Survival data was analyzed by Kaplan-Meier plotting and Cox regression.Results: One third of the cohort received blood transfusions during the period of NAC. In univariate analysis, blood transfusions during NAC, nodal stage and advanced tumor stage (pT >2) were negative prognostic factors for survival. In multivariate analysis, only pNx and pT >2 remained significant negative prognostic factors. In a subgroup analysis consisting of patients with localized tumors without dissemination (n = 96), patients that received transfusions during NAC showed an 18.5% absolute risk increase of death at five years of observation, although without statistical significance (p = .197).Conclusions: This is the first time that the extent and plausible effects of allogenic blood transfusions during NAC is examined in MIBC. Data suggest that there may be an association between blood transfusion and poor pathological and oncological outcome. Firm conclusions are difficult to draw due to few study participants and the retrospective nature of the study.	bladder
Malignancy after Augmentation Enterocystoplasty: A Nationwide Study of Natural History, Prognosis and Oncogene Panel Analysis.	PURPOSE: We report the natural history and prognosis of tumors after augmentation enterocystoplasty, with a molecular analysis using an oncogene panel to search for potential targeted therapies. MATERIALS AND METHODS: This multicenter, nationwide, retrospective study included 16 patients. A panel of 21 clinically relevant oncogenes was tested on archival tumor specimens using next-generation sequencing. Survival rate was the main clinical outcome and sequences were compared to the reference genome for the genetic outcome. RESULTS: Augmentation enterocystoplasties were performed mainly for congenital neurogenic bladder and bladder exstrophy at a median patient age of 17 years (range 4 months to 45 years). Most of the malignancies were diagnosed because of clinical manifestations, with a median latency period of 20 years. Adenocarcinomas were mainly found after gastrocystoplasty, whereas urothelial cell carcinomas were typically found after colocystoplasty. Of the 16 patients 13 were diagnosed at an advanced stage of the disease (positive lymph nodes in 7, distant metastases in 6). The overall 1-year survival rate was 56%. Only 3 patients remained disease-free at a median followup of 70 months. Of the 9 tumors with analyzable DNA 4 were wild-type and 5 harbored missense mutations (KIT-p.Pro573Ser, PDGFRA-p.Glu587Lys, KRAS-p.Gly12Asp, ERBB4p.Arg484Lys, CTNNB1-p.Ser37Phe and p.Ser47Asn). CONCLUSIONS: Malignancy after augmentation enterocystoplasty is diagnosed late with frequent metastases and a very low 1-year survival rate. More than half the tested samples harbored missense mutations in oncogenes accessible to targeted therapies. An international collaboration to enlarge the genetic panel analysis of these tumors may offer new therapeutic hope to patients.	bladder
miR-190b promotes tumor growth and metastasis via suppressing NLRC3 in bladder carcinoma.	Bladder cancer is one of the most common urogenital malignancies. However, its pathogenesis, especially molecular mechanisms remain elusive. Thus, understanding the molecular mechanisms underlying bladder cancer is important for the discovery of novel therapeutic paradigms for these diseases. In current study, we found that micro-RNA (miR)-190b is highly expressed in bladder cancer tissues and cells. Overexpression of miR-190b enhanced the proliferation, growth, migration and invasion capabilities, and angiogenesis of bladder cancer cells, whereas downregulation of miR-190b reversed these effects. Target prediction and dual luciferase reporter assays identified NLR family CARD domain containing 3 (NLRC3) as a potential target of miR-190b. Pathway analysis indicated that miR-190b promotes bladder cancer progression via the Wnt/β-catenin and mTOR signaling pathways. Taken together, our findings imply that miR-190b acts as a critical regulator for bladder cancer development by repressing NLRC3 and partly through the Wnt/β-catenin and mTOR pathways. Our study suggests that miR-190b may be served as a potential therapeutic target for bladder cancer treatment.	bladder
Competitive glucose metabolism as a target to boost bladder cancer immunotherapy.	Bladder cancer - the tenth most frequent cancer worldwide - has a heterogeneous natural history and clinical behaviour. The predominant histological subtype, urothelial bladder carcinoma, is characterized by high recurrence rates, progression and both primary and acquired resistance to platinum-based therapy, which impose a considerable economic burden on health-care systems and have substantial effects on the quality of life and the overall outcomes of patients with bladder cancer. The incidence of urothelial tumours is increasing owing to population growth and ageing, so novel therapeutic options are vital. Based on work by The Cancer Genome Atlas project, which has identified targetable vulnerabilities in bladder cancer, immune checkpoint inhibitors (ICIs) have arisen as an effective alternative for managing advanced disease. However, although ICIs have shown durable responses in a subset of patients with bladder cancer, the overall response rate is only ~15-25%, which increases the demand for biomarkers of response and therapeutic strategies that can overcome resistance to ICIs. In ICI non-responders, cancer cells use effective mechanisms to evade immune cell antitumour activity; the overlapping Warburg effect machinery of cancer and immune cells is a putative determinant of the immunosuppressive phenotype in bladder cancer. This energetic interplay between tumour and immune cells leads to metabolic competition in the tumour ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. Thus, molecular hallmarks of cancer cell metabolism are potential therapeutic targets, not only to eliminate malignant cells but also to boost the efficacy of immunotherapy. In this sense, integrating the targeting of tumour metabolism into immunotherapy design seems a rational approach to improve the therapeutic efficacy of ICIs.	bladder
A simplified nomogram to assess risk of bladder cancer in patients with a new diagnosis of microscopic hematuria.	INTRODUCTION: The vast majority of patients who undergo a diagnostic evaluation for microscopic hematuria (MH) do not have occult bladder cancer. Identifying patients with MH at high risk of harboring bladder cancer can allow for a risk adjusted approach to diagnostic interventions with the goal of safely reducing unnecessary evaluations. METHODS: Patients with a new diagnosis of microhematuria during an 8.5 year period were retrospectively identified. All patients who had a complete MH evaluation were randomized to a training or a validation cohort. Logistic regression analysis was performed in the training cohort to identify factors related to a bladder cancer diagnosis and to develop our model. Receiver operating curves to identify bladder cancer were constructed for the training and validation cohort and tested for their ability to discriminate true cases. A nomogram to predict a bladder cancer diagnosis was created. RESULTS: In 4,178 patients split into training and validation cohorts, those diagnosed with bladder cancer were shown to be older, have a greater degree of MH (more RBC/hpf), and were former or current smokers. A nomogram created using this model was able to predict risk of a bladder cancer diagnosis with good discrimination (areas under the curve 0.79, 95% CI 0.75-0.83). A cutoff of 0.01 probability demonstrated a sensitivity of 99.1% and a negative predictive value of 99.7%. CONCLUSION: A nomogram can accurately predict the risk of bladder cancer diagnosed during the evaluation of MH and can potentially be used avoid a significant number of work ups in those at the lowest risk.	bladder
Enhanced Efficacy of PEGylated Liposomal Cisplatin: In Vitro and In Vivo Evaluation.	This study aims to evaluate the potency of cisplatin (Cispt)-loaded liposome (LCispt) and PEGylated liposome (PLCispt) as therapeutic nanoformulations in the treatment of bladder cancer (BC). Cispt was loaded into liposomes using reverse-phase evaporation method, and the formulations were characterized using dynamic light scattering, scanning electron microscopy, dialysis membrane, and Fourier-transform infrared spectroscopy (FTIR) methods. The results showed that the particles were formed in spherical monodispersed shapes with a nanoscale size (221-274 nm) and controlled drug release profile. The cytotoxicity effects of LCispt and PLCispt were assessed in an in vitro environment, and the results demonstrated that PLCispt caused a 2.4- and 1.9-fold increase in the cytotoxicity effects of Cispt after 24 and 48 h, respectively. The therapeutic and toxicity effects of the formulations were also assessed on BC-bearing rats. The results showed that PLCispt caused a 4.8-fold increase in the drug efficacy (tumor volume of 11 ± 0.5 and 2.3 ± 0.1 mm(3) in Cispt and PLCispt receiver rats, respectively) and a 3.3-fold decrease in the toxicity effects of the drug (bodyweight gains of 3% and 10% in Cispt and PLCispt receiver rats, respectively). The results of toxicity were also confirmed by histopathological studies. Overall, this study suggests that the PEGylation of LCispt is a promising approach to achieve a nanoformulation with enhanced anticancer effects and reduced toxicity compared to Cispt for the treatment of BC.	bladder
[Open vs Laparoscopic Radical Cystectomy: Comparison of perioperative and Mid-term oncological outcomes.].	OBJECTIVE: To compare peri-operative and mid-term oncological outcomes between Open radical cystectomy (ORC) and Laparoscopic radical cystectomy (LRC). METHODS: A retrospective cohort was assembled, in which 182 patients had been subjected consecutively to Radical Cystectomy (RC) for treatment of muscle-invasive bladder cancer (MIBC) between 2000 and 2010 in a single center. Two cohorts were included: ORC (n=83) and LRC (n=99). All the RCs were performed by the same surgeon. Perioperatory complications were registered according to Clavien-Dindo classification. We evaluated recurrence-free survival, cancer-specific survival and association between the surgical technique performed and disease recurrence, with co-variable adjustment. RESULTS: Clinical and pathologic characteristics were similar for both groups. Significant differences were observed between the two groups, regarding blood loss, operative time and hospitalization days (p<0.04). The ORC group displayed 27 (32.5%) Clavien I-II cases, vs. 11 (11.1%) in the LRC group. Four Clavien≥III (4.8%) complications were reported in the ORC, vs. 7 (7%) in the LRC group (NS). Mean follow-up time for patients without recurrence was 23 months (12-48). A total of 60 patients (72.3%) showed recurrence in the ORC group, compared to 59 (59.6%) in the LRC group. Cumulative cancer-specific mortality index, stratified by surgical technique, was similar between both groups (p.-0.9). CONCLUSIONS: Based on our experience, LRC showed advantages in intraoperative bleeding and length of hospital stay with no difference in major complications between both groups. Mid-term oncological control, regarding local recurrence and cancer-specific survival, showed no significant difference between LRC and ORC in the management of MIBC.	bladder
Risk-adapted management of low-grade bladder tumours: recommendations from the International Bladder Cancer Group (IBCG).	OBJECTIVE: To provide a contemporary update and recommendations for the diagnosis and management of low-grade non-muscle-invasive bladder cancer (BCa) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses and reviews (up to March 2019) and provide recommendations on baseline evaluations, treatment, endpoints, study design and surveillance protocols. RESULTS: Low-grade Ta BCa poses minimal risk to patients in terms of progression and disease-specific survival. Thus, to minimize patient morbidity, this entity should be managed appropriately. After initial diagnosis of low-grade Ta tumour, subsequent stable, low-grade-appearing recurrences can be managed conservatively with office cystoscopy and fulguration or even followed using an active surveillance protocol. Intravesical therapy other than single-dose peri-operative chemotherapy instillation should be used judiciously, and only after assigning appropriate risk points. Routine use of urinary cytology - other than at initial risk stratification, or for patients on active surveillance without therapy - is not recommended; and surveillance cystoscopy may be discontinued after 5 years. Clinical studies in this group of patients should focus on recurrence rates, and time to recurrence, rather than progression events. CONCLUSIONS: The International Bladder Cancer Group has developed formal recommendations regarding the diagnosis, treatment and surveillance of low-grade non-muscle-invasive BCa to minimize morbidity and encourage uniformity among studies in this disease.	bladder
Incidental sonographic detection of bladder cancer in a woman with large uterine fibroids: significance and lessons learned.	Uterine leiomyomas are the most common solid pelvic tumors in pre-menopausal women and typically present with abnormal uterine bleeding and/or symptoms of mass effect. A potential consequence of the space-occupying nature of these lesions is the decreased sensitivity for the detection of adjacent pelvic pathology, which can be particularly problematic given the overlap in symptoms between fibroids and other pelvic disease. We present the case of a woman with a large uterine fibroid who had multiple imaging evaluations before undergoing uterine fibroid embolization and on immediate follow-up sonography was discovered to have early-stage bladder cancer.	bladder
Oncological outcomes and recurrence patterns after laparoscopic radical cystectomy for bladder cancer: A Japanese multicenter cohort.	OBJECTIVE: To investigate oncological outcomes and recurrence patterns after laparoscopic radical cystectomy for bladder cancer in a Japanese multicenter cohort, and to explore the risk factors associated with recurrences due to tumor dissemination. METHOD: Laparoscopic radical cystectomies carried out at 10 institutions were included in this retrospective study. Multivariate analyses were carried out to identify the clinical parameters associated with overall recurrences together with specific recurrence types. Kaplan-Meier curves were created to elucidate time to recurrence and survival. RESULTS: A total of 411 patients were included after the final analysis. Postoperative pathology was T2 or higher in 196 patients (48%), and lymph node metastasis was present in 46 patients (11%). The median follow-up period was 23 months, and the 2-year recurrence-free and cancer-specific survival rates were 71.0% and 84.7%, respectively. The recurrence sites involved distant metastasis in 75 patients (18%), local recurrence in 52 patients (13%) and urinary tract recurrence in eight patients (2%). When local recurrence at the cystectomy bed (28 patients; 7%) and abdominal recurrence including peritoneal carcinomatosis or port site recurrence (17 patients; 4%), which might be caused by tumor dissemination, were combined into a single group, prolonged surgical time was a significant risk factor, in addition to high pathological stage (T3-4 and/or positive lymph nodes), positive surgical margins, and variant histology by both univariate and multivariate analyses. CONCLUSIONS: Our study findings suggest that recurrences after laparoscopic radical cystectomy might be caused by tumor dissemination, and attention should be paid to avoid prolonged surgical time in laparoscopic radical cystectomy.	bladder
Bladder cancer genomics.	Until recently, the treatment of bladder cancer, for several years, was limited to surgery and to immunotherapy or chemotherapy. Currently, the extensive analysis of molecular alterations has led to novel treatment approaches. The advent of polymerase chain reaction and genomic hybridization techniques has allowed to investigate alterations involved in bladder cancer at DNA level. By this way, bladder cancers can be classified as papillary or non-papillary based on genetic alterations with activation or mutations in FGFR3 papillary tumors and with inactivation or mutations involving TP53 and RB1 in non-papillary tumors. Recently, the patterns of gene expression allow to differentiate basal and luminal subtypes as reported in breast cancer. In particular, basal cancers are composed of squamous and sarcomatoid pathological findings, while luminal cancers are composed of papillary finding features and genetic mutations (FGFR3). In particular, specific investigative studies demonstrated that luminal cancers are associated with secondary muscle invasive cancer while basal tumors are related to advanced disease since they are often metastatic at diagnosis. Moreover, from therapeutic point of view, different researchers showed that mutations of DNA are related to the sensitivity of bladder cancer while performing cisplatin chemotherapy. In this prospective, the bladder cancer molecular subtyping classification might allow identifying the set of patients who can safely avoid neoadjuvant chemotherapy likely because of the low response to systemic chemotherapy (chemoresistant tumors). In this context, the Cancer Genome Atlas (TCGA) project has improved the knowledge of the molecular targets of invasive urothelial cancers allowing the researchers to propose hypothesis suggesting that agents targeting the genomic alterations may be an effective strategy in managing these cancers, which occur in about 68% of muscle invasive cancers. A future goal will be to combine treatment strategies of invasive bladder cancers according to their genetic mutational load defined by molecular pathology.	bladder
Oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in Denmark.	Objective: To report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large study sample.Materials and methods: This was a nationwide multicenter registry-based cohort study of all patients with upper urinary tract urothelial neoplasia in Denmark found to be eligible for nephroureterectomy between April 2004 and April 2017 (N = 1384). Primary endpoints were intravesical recurrence-free survival and overall survival. Survival probabilities were estimated with Kaplan-Meier and the log-rank test to compare survival curves. Association with clinical outcomes was studied using univariate and multivariate Cox proportional hazards.Results: Intravesical recurrence-free survival was 72% [95% confidence interval (CI) 69-75%] at 5 years and 70% (95% CI 67-73%) at 10 years. Patients with muscle-invasive disease had a significantly lower rate of intravesical recurrence [hazard ratio (HR) = 0.46, p < 0.0001] and patients with high-grade tumors had a significantly higher rate of incident intravesical recurrence compared to low-grade tumors (HR = 1.65, p = 0.001). The overall survival was 76% (95% CI 74-79%) at 5 years and 64% (95% CI 60-70%) at 10 years. Patients with higher age (p = 0.008) and muscle-invasive disease (p < 0.0001) had worse overall survival. When comparing surgical approaches, laparoscopic nephroureterectomy versus open nephroureterectomy did not differ in intravesical recurrence-free survival but was associated with shorter postoperative hospital stay (p < 0.0001) and better overall survival (p = 0.02).Conclusions: We report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large sample and give insights into predictive factors with significant impact.	bladder